@article {Charoentong056101, author = {Pornpimol Charoentong and Francesca Finotello and Mihaela Angelova and Clemens Mayer and Mirjana Efremova and Dietmar Rieder and Hubert Hackl and Zlatko Trajanoski}, title = {Pan-cancer immunogenomic analyses reveal genotype-immunophenotype relationships and predictors of response to checkpoint blockade}, elocation-id = {056101}, year = {2016}, doi = {10.1101/056101}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Current major challenges in cancer immunotherapy include identification of patients likely to respond to therapy and development of strategies to treat non-responders. To address these problems and facilitate understanding of the tumor-immune cell interactions we inferred the cellular composition and functional orientation of immune infiltrates, and characterized tumor antigens in 19 solid cancers from The Cancer Genome Atlas (TCGA). Decomposition of immune infiltrates revealed prognostic cellular profiles for distinct cancers, and showed that the tumor genotypes determine immunophenotypes and tumor escape mechanisms. The genotype-immunophenotype relationships were evident at the high-level view (mutational load, tumor heterogenity) and at the low-level view (mutational origin) of the genomic landscapes. Using random forest approach we identified determinants of immunogenicity and developed an immunophenoscore based on the infiltration of immune subsets and expression of immunomodulatory molecules. The immunophenoscore predicted response to immunotherapy with anti-CTLA-4 and anti-PD-1 antibodies in two validation cohorts. Our findings and the database we developed (TCIA-The Cancer Immunome Atlas, http://tcia.at) may help informing cancer immunotherapy and facilitate the development of precision immuno-oncology.}, URL = {https://www.biorxiv.org/content/early/2016/05/31/056101}, eprint = {https://www.biorxiv.org/content/early/2016/05/31/056101.full.pdf}, journal = {bioRxiv} }